Radical treatments of type 1 diabetes include, for example, pancreas transplantation from a brain-dead donor. The pancreas transplantation has a significant efficacy such as enabling insulin independence by single transplantation. However, the transplantation has a problem of placing a large burden on the body of recipients because it involves a complicated surgery and revascularization, and also, it has the possibility of inducing complications. Accordingly, attention has been focusing on islet transplantation as a new radical treatment of diabetes in recent years. The islet transplantation is a method which involves isolating islets, which are tissues secreting insulin and glucagon as hormones regulating blood sugar, from the pancreas and transplanting the isolated islets into the liver through the portal vein. The transplanted islets are engrafted at the end of the portal vein in the liver, which can secrete insulin.
Whereas conventional pancreas transplantation is a surgical procedure involving extensive invasiveness, the islet transplantation has less surgical stress on the body of recipients and is safe compared to the pancreas transplantation because it requires only a procedure involving leaving a catheter in the portal vein and transplanting islets in the same manner as drip infusion. The islet transplantation is also a kind of cell transplantation unlike other organ transplantations; thus, the semi-permanent frozen storage of islets therefore is possible. In addition, the islet transplantation has the advantage of not requiring it to take the trouble to excise cells even if rejection occurs, because the transplanted islets themselves are absorbed.
However, the islet transplantation has the disadvantage of shortage of islets suitable for transplantation because of the technical difficulty in isolation only of islet cells from the pancreas. As a result, a plurality of transplantations are necessary until insulin independence is achieved, requiring pancreas donations from 2.6 donors on average for one recipient. Accordingly, it is a challenge how to obtain many islets of good quality from the pancreas.
To overcome this challenge, various methods for isolating islets have previously been studied. For example, Patent Document 1 discloses a method for isolating islets, comprising injecting a protective solution containing a protease inhibitor into the pancreatic duct in advance. In the method for isolating islets, the protease inhibitor is used to improve the yield of the islets.
For conventional methods for isolating islets, the cause of not providing islets of sufficient quality and yield is considered to be that endogenous enzymes derived from the exocrine pancreas present in the pancreas are activated by the excision of the pancreas and damage pancreatic tissue, as disclosed in Non Patent Document 1; the above method for isolating islets of Patent Document 1 contemplates the improvement of the quality and yield of the islets by inhibiting the activity of the endogenous enzymes. Examples of the enzymes derived from the exocrine pancreas are trypsin, pancreas-derived elastase, and chymotrypsin; the above Patent Document 1 uses urinastatin, which specifically inhibits trypsin.
Patent Document 1 describes that the appropriate protection of islet tissue by a protease inhibitor results in the increased yield of islets. However, conventional methods often cause the physical damage of islet cells, such as being torn off, during isolation, and have not stably provided islets having a size and shape enough to secrete insulin after transplantation to necessary yields. Also, the urinastatin used as a protease inhibitor in Patent Document 1 has a problem of posing a high risk on a living body and lacking in safety because it is a biological preparation obtained using human urine as a raw material.